System and method for personalized injection treatment

ABSTRACT

An automated system (100) for compounding pharmaceutical agents for injection treatment of a patient includes a housing (110) enclosing an interior space; an inventory structure (130) having a plurality of chambers (131) for individually holding one or more pharmaceutical agent—containing single use capsules (102), wherein each capsule has a volume capacity of from about 0.1 to about 10.0 mL liquid; means (140) for selecting capsules in accordance with predetermined pharmaceutical agents contained in said capsules; means (150) for moving the selected capsules to a processing area; means (165,166) for sequentially transferring a controlled quantity of the predetermined pharmaceutical agent with direct fluid communication from each selected capsule to a product container under positive or negative pressure; and means (151) for automatically discarding spent capsules from which the pharmaceutical agents have been removed after a single use.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation-in-part of U.S. applicationSer. No. 13/982,213, the entire contents of which are incorporated byreference. This application also claims priority to U.S. ProvisionalApplication Ser. No. 61/437,152 filed Jan. 28, 2011, which is hereinincorporated by reference in its entirety.

BACKGROUND 1. Field of the Invention

The present invention relates to a system and method for personalizingan injection treatment for administering pharmaceutical agents to apatient.

2. Background of the Art

Americans are increasingly aware of the health environment, availabledrugs, and information technology. They demand that disease preventionand treatment should be tailored for the individual's need, wherepossible.

There is a greater benefit to administer injectable combinations ofpharmaceutical agents such as vitamins, growth hormones, glucosamine,omega-3 fatty acids, insulin and other such agents. When a medication isadministered orally, the bioavailability (i.e., the fraction of theingested dose which is actually absorbed) of such agents significantlydecreases due to incomplete absorption and first-pass metabolism, whichmay vary from patient to patient. However, the bioavailability of agentsadministered intravenously can be up to 100%. Also, it is reported that15% of the population cannot properly absorb vitamins and other oralmedications if administered orally. Moreover, since the medicationrequirements can vary from patient to patient, it is necessary todevelop a personalized formulation of pharmaceutical agents in aninjection to meet the needs of the patent.

British researchers say tumors begin to shrivel within 24 hours ofinjecting a vitamin E extract into patients. After ten days the tumorshave almost disappeared According to Jane Higdon, Ph.D. of Oregon StateUniversity, there is currently no evidence in humans that taking oralalpha-tocopheryl succinate supplements delivers alpha-tocopherylsuccinate to tissues Research has suggested that the bioavailability ofVitamin E from natural sources is twice that of synthetic sources.Furthermore, it is important to note that studies of patients with fatmalabsorption have shown that vitamin E absorption requires normaldigestive processes involved in the absorption of dietary fats. Linkingoral vitamin E ingestion to the proper absorption of dietary fatscomplicates matters because the amounts and forms of fat required foroptimal vitamin E absorption are unknown.

Similarly, gastrointestinal absorption of vitamin B12 depends on thepresence of sufficient intrinsic factor and calcium ions. While oralabsorption is considered too unreliable in patients with perniciousanemia or other conditions, an injection of vitamin B12 may prevent theprogression of neurologic damage in severe cases. Parenteraladministration of vitamin B12 treat a variety of conditions includingpernicious anema, age related vitamin B12 deficiencies, lessens severityof Alzheimer's disease, reverse/contain cases of senile dementia,therapeutic value in treating Autism/ADD, and Multiple Sclerosis.Reportedly, 94% of children with symptomatic of autism spectrumdisorders respond to Methyl-B12 therapy (vitamin B12 injections).

Various systems are known for compounding various pharmaceuticaladmixtures in a single container. See, e.g., U.S. Pat. Nos. 7,610,115,7,194,336, 7,171,992, 6,975,924, 6,951,228, 5,697,407, 5,431,202,5,085,256, 5,040,699, 4,922,975, 4,789,014, 4,653,010, 4,513,796, and4,467,844 for various fluid transfer and compounding systems.

However, there is a significant pharmacoeconomic gap betweenprescription drug treatments with pharmaceutical agents and generalself-care with currently available pharmaceuticals. What is needed is asystem usable in a physician's office or clinic to enable a personalizedtreatment of patients with individually compounded admixtures ofpharmaceuticals, biologics, or injectables either intravenously (IV),intramuscularly (IM) or subcutaneously. Further needed is a systemincorporating the latest information technology employing, for example,wireless, software, and/or secured Internet based communication systems.

SUMMARY

An automated system for compounding pharmaceutical agents for injectiontreatment of a patient is provided herein. The system comprises: ahousing enclosing an interior space; an inventory structure having aplurality of chambers for individually holding one or morepharmaceutical agent-containing single use capsules, wherein eachcapsule has a volume capacity of from about 0.1 to about 10.0 mL liquid;means for selecting capsules in accordance with predeterminedpharmaceutical agents contained in said capsules; means for moving theselected capsules to a processing area; means for sequentiallytransferring a controlled quantity of the predetermined pharmaceuticalagent with direct fluid communication from each selected capsule to aproduct container such as a product vial or a syringe under positive ornegative pressure; and means for automatically discarding spent capsulesfrom which the pharmaceutical agents have been removed after a singleuse.

This innovative technology will enable a novel personalized medicineplatform where the personalized medicine opportunity can be implemented,it can be used to safely and efficiently expand physician services,improve treatment and improve outcomes. This device is applicable forpatients requiring effective doses of treatment combinations ofvitamins, growth hormone, glucosamine, omega-3, onabotulinumtoxin A,insulin and other agents that are used for in-office injection.

Other embodiments of the present invention include compounding agentsfor the topical treatment of a patient or subject. Topical treatmentincludes the application of the resulting compounded product to the skinof a patient or subject. The agents being compounded can bepharmaceutical agents to be used in treating skin conditions and/ordiseases. Alternatively, the agents being compounded can benon-pharmaceutical agents that are used in over the counter skincareproducts. In addition, the agents being compounded can be a combinationof pharmaceutical agents and non-pharmaceutical agents.

With regard to the above embodiments, the term “pharmaceutical agent(s)”as it appears in this specification can also represent anon-pharmaceutical agent (i.e., “agent(s)”). Also, the term “patient” asit appears in this specification includes subjects not necessarily beingtreated for any medical condition (e.g., the subject can simply be aperson using a skincare product).

The system described herein as being used for compounding pharmaceuticalagents for injection treatment can also be used for compounding agentsfor topical treatment.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments are described below with reference to the drawingswherein:

FIG. 1 is a perspective view illustrating one embodiment of theinvention;

FIGS. 2A-2D illustrate preparation of a product vial by mounting aconnector and cap thereto;

FIGS. 3A and 3B are, respectively, front and rear perspective views ofthe interior of the apparatus of the invention;

FIG. 4 is a perspective view of a channel member;

FIG. 5 illustrates a pharmaceutical agent-containing capsule;

FIGS. 6 and 7 illustrate, respectively, the movement of a sliding gate141 at the bottom of the channel member to release a capsule from thebottom of the channel member;

FIGS. 8 and 9 are interior perspective views illustrating the conveyormeans for moving capsules into a processing area;

FIGS. 10A and 10B are perspective views of the means for puncturing thecapsule which include a movable platform for raising the product vialwith attached connector from a lower position (FIG. 10A) to an upperposition (FIG. 10B) wherein the needle of the connector cap pierces thepharmaceutical agent-containing capsule;

FIG. 11 illustrates caliper means for applying positive outside pressureto compress the capsule and force pharmaceutical agent into theprocessing vial;

FIG. 12 is a plan view of the caliper and capsule;

FIGS. 13A and 13B are, respectively, perspective and elevational viewsillustrating the disposal of the spent capsule into the discard bin;

FIGS. 14 A and 14B are perspective views of another embodiment of theinvention;

FIG. 15 is an interior view of the embodiment of FIGS. 14A and 14B;

FIG. 16 illustrates a pharmaceutical agent-containing capsule;

FIG. 17 is a perspective view illustrating the loading of the capsuleinto the apparatus of the invention;

FIG. 18 is a perspective view of an inventory structure;

FIG. 19 illustrates a hypodermic syringe;

FIG. 20 illustrates the loading of the hypodermic syringe into theapparatus of the invention;

FIGS. 21 and 22 illustrate the positioning of the hypodermic syringeinto the syringe station;

FIGS. 23 and 24 illustrate the arrangement of the carousel, workingcylinder, and blocking plate;

FIGS. 25A to 25G illustrate the removal of as cap from a hypodermicsyringe, the puncturing of the capsule and loading of the hypodermicsyringe with the pharmaceutical agent;

FIG. 26 illustrates the blocking plate with an open gate;

FIG. 27 illustrates the blocking plate with open gate arranged for thedisposal of a spent capsule into the spent capsule discard bin;

FIG. 28 is a perspective view of another embodiment of the systemapparatus of the invention;

FIGS. 29A and 29B are perspective views of the interior of theembodiment shown in FIG. 28;

FIG. 30 illustrates the loading of a capsule into the carousel;

FIG. 31 is a perspective view of the working cylinder and blocking plateas well as the means for puncturing the capsule and disposal of thecapsule;

FIGS. 32A and 32B are plan views illustrating the puncturing of thecapsule by the extraction needle;

FIGS. 33A and 33B illustrate the transfer of the pharmaceutical agentinto the product vial;

FIGS. 34A and 34B illustrate the disposal of waste solution;

FIG. 35 illustrates an alternative configuration of the pharmaceuticalagent-containing capsule;

FIG. 36 illustrates the application of positive pressure in a verticaldirection to a capsule to expel pharmaceutical agent therefrom;

FIGS. 37A and 37B illustrate the application of lateral positivepressure to a capsule to expel pharmaceutical agent therefrom;

FIGS. 38 to 43D illustrate the placement of sensors in the systemapparatus of the invention to monitor the positioning of capsules andvarious components of the apparatus; and,

FIG. 44 illustrates the loading of linear channel members into acarousel shaped inventory structure.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT(S)

Other than in the working examples or where otherwise indicated, allnumbers expressing amounts of materials, reaction conditions, timedurations, quantified properties of materials, and so forth, stated inthe specification and claims are to be understood as being modified inall instances by the term “about.”

It will also be understood that any numerical range recited herein isintended to include all sub-ranges within that range.

It will be further understood that any compound, material or substancewhich is expressly or implicitly disclosed in the specification and/orrecited in a claim as belonging to a group of structurally,compositionally and/or functionally related compounds, materials orsubstances includes individual representatives of the group and allcombinations thereof.

This system and method for personalized injection treatment issynchronized with a complementary health management system (acomputerized and networkable via wireless or wired connection) and willautomatically compound and record patient specific doses of injectablemedicine for disease prevention and/or treatment and the patient'sprogress will be monitored on the Internet longitudinally. The term“patient” herein can mean a sick or healthy human or animal (e.g.,mammals such as dogs, cats, pigs, horses or cattle). The term“pharmaceutical agent” as used herein refers to an injectable solutionproviding health benefits and/or a therapeutic effect and or therapeuticpotency including, but not limited to a vitamin, a drug, aneutraceutical, a biologic or any combination thereof. The inventionherein will compound the components with the customized, personalizeddosage proportion, and then prepare a single product container such as aproduct vial or syringe for injection. The size of the invention may besimilar to those gourmet single cup coffee machines or inkjet/laserprinters. The proportion is determined by the physician or an Internettool that is scientifically validated. A physician may make apersonalized compounding order for injectable solutions such asvitamins, growth hormone, glucosamine, omega-3, onabotulinumtoxin A(e.g., BOTOX®) and insulin through communication devices such as acomputer, a PDA, or a smart phone. Operators such as physicians ornurses may input a compounding order directly and manually with using acontrol pad and the system may have a control screen such LED and LCDmonitor. Alternately, the system can have a touch screen unit combiningdisplay and input units. When the single product container is created,the optimizer will input the patient record into the serversimultaneously. The patient may have received a set of codes in advancevia an Internet tool and may bring in the print-out for the physician.An inventory structure can have a plurality of vertical chambersindividually holding one or more pharmaceutical agent-containingcapsules. Each chamber can typically store 10 to 30 capsules. Thecapsules can have a volume capacity of about 0.1 to about 10.0 mL,preferably 0.1 mL to about 2.0 mL liquid, and most preferably about 1.0mL liquid. The pharmaceutical agent-containing capsules and the chamberspreferably will be clearly labeled and color coded. Once thepharmaceutical agent-containing capsules are loaded into the device, itwill compound the exact proportion into a single injection productcontainer. The delivery components are thoroughly sterilized and anempty product container can be loaded by an operator. The productcontainer can have a volume capacity of about 0.1 to about 10.0 mL andtypically about 2.0 mL liquid. The capsules and product container can becompletely or partially filled with the pharmaceutical agent. Dependingon the compounding order, the capsules can be selectively loaded andtransported to a processing area. At the processing area, the selectedcapsules can be connected to the product container and a quantity of thepredetermined pharmaceutical agent can be transferred to the productcontainer under positive or negative pressure. The positive pressure canbe generated by mechanical compress outside the selected capsules andthe negative pressure inside the selected capsules can be employed by avacuum pump or syringe in order to draw the pharmaceutical agent out ofthe capsule. Alternatively, the capsules can be properly pressurized andpackaged so that inside solution may automatically come out withoutauxiliary pressurization. The transferring quantity can be controlled byregulating amount of the applied pressure and time. The consumedmedicine capsules are disposed of automatically after a single use. Thesolution inside the capsules can be transferred through a connector,which is pre-assembled with a product vial as a cap before it is placedinto the system and consisted of a needle and an air vent.Alternatively, the solution can be transferred through an extractionneedle engaged with the loaded capsules and an injection system engagedwith the product vial. The system may be enclosed by a housing and anair ventilation system may be included in the apparatus. All of theembodiments described below can include sterilization means such as UVlamps to provide an internal aseptic environment. A plurality sensorssuch as proximity sensors, distance sensors, and temperature sensors maybe placed in order to monitor if desired capsules are loaded, in orderto monitor if the system operates properly in order to check if thegate/door is closed, and also in order to monitor temperature inside thesystem. Sensors can be used in each of the embodiments described belowand are commercially available, for example, from Sharp in Japan,Keyence Corporation of America in Itasca, Ill., Automation Direct in theU.S., and c3controls in the U.S. After all processes are completed, theproduct container can be taken out by an operator. Labels which includepatient information and compounding order with text, bar code, or QRcode format, can be printed out and the labels will be attached on theproduct container and the patient chart.

Referring now to FIGS. 1 to 13B, an embodiment of the system apparatus100 of the invention for compounding pharmaceutical agents isillustrated.

FIG. 1 illustrates a housing 110 having a top surface with a lid 111 forallowing access for loading pharmaceutical agent-containing capsulesinto the system apparatus. The housing 110 includes a liquid crystaldisplay (LCD) screen 112 on a front wall for providing information tothe user as to the status and operation of the system. The front wallcan also include a key pad 113 for data entry and the input of operatinginstructions. Alternatively, the system apparatus 100, as well as theembodiments described below, can include touch screens which includefunctions of information display and input of instructions/information.A side surface also includes a door 114 for a label printer, the printedlabel being issued from slot 115 on the front wall of the housing. Vialloading door 119 provides access for loading an empty product vial intoa product vial chamber 116 and removal of the filled product vialtherefrom. Door 117 provides access to a spent capsule disposal bin forremoval from the system apparatus. Electrical components andmicroprocessor(s) are contained in the rear sections 118 of theapparatus 100 which can be opened to provide access thereto.

The invention includes a system also responsive to instructions providedremotely by computer/PDA/smart phones and the like by cable, Bluetooth,or internet protocol/transmission control protocol (IP/TCP). Suchinstructions relate to the type and amounts of pharmaceutical agents areto be compounded for the patent as well as appropriate patientinformation.

Referring now to FIGS. 2A-2D a product vial 103 having a liquid volumecapacity of preferably about 2.0 mL, is prepared for filling byattachment thereto of a connector cap 170. The connector cap includes aneedle 171 and an air vent 172 and seals the top 104 of the product vial103. The pharmaceutical agents are compounded in the product vial 103which is then used for injection treatment of a patient. A protectivecap 175 is mounted to the connector cap 170 after the product vial hasbeen loaded with pharmaceutical agent to prevent accidental needle stabsin handling the product vial 103. The connector cap 170 includes anaccess port 173 through which a hypodermic syringe needle can beinserted to load the pharmaceutical agent composition onto thehypodermic syringe for subsequent injection into a patient. Protectivecap 175 has a similar access port 176. The access ports 173 and 176include a resilient material such as rubber, which is penetrable by thehypodermic needle, but which seals the port after withdrawal of thehypodermic needle.

Referring now to FIGS. 3A-3B, in an embodiment of the invention frame120 surrounds and supports the internal mechanism of the systemapparatus 100. Frame 120 can be fabricated from metals such as ferrousalloys or aluminum, or engineering plastics such as, for example,acrylonitrile butadiene styrene (ABS), polycarbonates (PC), polyamides(PA), polybutylene terephthalate (PBT), polyethylene terephthalate(PET), polyphenylene oxide (PPO), polysulphone (PSU), polyetherketone(PEK), polyetheretherketone (PEEK), polyimides, polyphenylene sulfide(PPS), and polyoxymethylene plastic (POM). Upper, middle and lowerlevels of the apparatus are at least partially delimited or defined byupper platform 121, middle platform 122 and lower, platform 123. Aninventory structure 130 is supported on upper platform 121 as well as alabel printer 108 and UV lamps 107 for sterilization of the environment.Temperature sensors (not shown in the figure) can be placed inside thesystem in order to monitor if the system is over heated. The inventorystructure includes a plurality of chambers such as vertical racks 131 inparallel arrangement. The racks each include a linear interior spaceadapted to slidably receive a corresponding channel member 132 (FIG. 4).The channel members 132 are each adapted to receive and store aplurality of pharmaceutical agent-containing capsules 102 (FIG. 5).Capsules 102 each have a cylindrical body 102 a and a hemispheric endportion 102 b, and are fabricated from a flexible polymeric materialwhich can be punctured by a needle but which is strong enough towithstand normal handling stresses without breaking or fracturing, andpreventing tear propagation and leaking after puncture. The capsules102, racks 131 and/or channel members 132 can be color coded oridentified by bar codes so that the proper pharmaceutical agents areloaded into the racks 131. The channel members 132 each include anelongated body having side rails 133 configured to slidably engagecorresponding linear notches in the interior side surfaces of the racks131. The channel members 132 also include laterally extending wings 134at the top of the body to facility grasping by a user's fingers. Acapsule separation system 141 described below engages a slot in thebottom portion of each channel member 132.

Referring to FIGS. 6 and 7, the system apparatus 100 includes means forselecting capsules in accordance with the pharmaceutical agentscontained therein. The selection means 140 include a capsule separationsystem 141, and a motor 142 for moving the capsule separation system141. The capsule separation system includes upper gate 141 a and lowergate 141 b slidably movable along guide rails 144. The separation system141 further includes a blocking plate 145 mounted to the upper gate 141a and slidably movable in and out of slot 136 in the channel member 132.The capsule separation system is slidably movable between a firstposition in which the upper panel blocking plate 145 is fully engagedwith the slot 136 in the respective channel member 132 so as to preventany capsules 102 from exiting the channel member 132 from the bottomthereof (FIG. 6), and a second position wherein the blocking plate 145is moved outside of the slot 136 in the channel member 132. However, inthe second position the lower gate 141 b is moved below the bottom ofthe channel member 132 to prevent the capsule from dropping further. Thecapsule separation system 141 is then moved back to the first positionand the selected capsule 102 is allowed to exit the bottom of thechannel member 132, but the blocking plate 145 is now in the firstposition which prevents another capsule from moving lower. The spacebetween the blocking plate 145 and the lower gate 141 b accommodatesonly a single capsule. Accordingly the back and forth motion of capsuleseparation system 141 limits the exiting of the capsules 102 from thebottom of the channel member 132 to one capsule at a time. Motor 142moves gate 141 in response to instructions for selecting thepharmaceutical agent contained in the capsules 102 loaded in the rack131. The operation of the motor 142 is adjusted to permit only a singlecapsule 102 to be released at a time. The released capsule 102 thenfalls into a chute 143 which directs the capsule 102 onto a lineartransport system as described below. Each rack 131 includes its ownmotor and capsule separation system.

Referring to FIGS. 8 and 9, the system 100 includes a linear transportsystem 150 as means for moving the capsules 102 to a processing area,said means including a chute 153 associated with each rack 131, aconveyor belt or chain 151 and capsule holders 152 fixedly mounted torespective saddling plates 155, which are in turn mounted to theconveyor belt/chain 151, and also a linear actuator 156 (FIGS. 3A and3B). Each capsule 102 is dropped through a respective chute 143 into arespective capsule holder 152 having a hemispheric cavity to accommodatethe hemispheric end 102 b of the capsule, which is then linearly movedto a processing area in which the capsules 102 are individuallypunctured and compressed to force the liquid contents of the capsules102 into the product vial 103. Guide channel 154 (FIG. 8) maintains thecapsules in the proper orientation and position while being moved.

Referring to FIGS. 10A and 10B, the processing area includes means forpuncturing the capsules 102 and means for transferring a quantity of thepharmaceutical agent from the capsule to the product vial 103.

More specifically, the puncturing of the capsule 102 is accomplished byloading the product vial 103 with the connector cap 170 attached theretointo a product vial chamber 116 and onto a product vial loading platform161. The loading platform 161 is then laterally moved to align theproduct vial 103 with the capsule 102. A motorized cranking member 162,in response to appropriate operating instructions, lifts the productvial 103 vertically upward until the needle 171 punctures the end 102 bof the capsule 102, thereby permitting fluid communication therewith.

Referring to FIGS. 11 and 12, the means for transferring thepharmaceutical agent from the capsule 102 to the product vial 103includes calipers 165 having jaws 166 movable between an open positionto a closed position in response to appropriate operating instructions.The jaws 166 each have a soft pad 168, which contacts the capsule 102.Cable 169 can be connected to arms 166 a and when pulled by motor 195 asshown by the arrow, cable 169 closes the jaws 166. In the closedposition the jaws apply external pressure to the side 102 a of capsule102, which forces fluid pharmaceutical agent through the bore of needle171 and into the product vial 103. A quantity of the transferredsolution can be determined by controlling the applied external pressure,which is regulated by pulling force or distance of the cable 169. Vent172 in the connector cap 170 permits air to escape from the product vial103 as it is being filled. After the processing of a capsule containingone pharmaceutical agent is completed another capsule containing anotherpharmaceutical agent is moved into the processing area for the sameprocedure until all of the selected pharmaceutical agents have beencompounded.

Referring to FIGS. 13A and 13B, the system includes means forautomatically discarding the spent capsules 102, which includes a spentcapsule waste bin 180 positioned at an end of the processing area. Theconveyor belt 151 advances the spent capsule to the end of the conveyorsystem 150 wherein the belt turns downward and the spent capsule isdropped into the bin 180. The bin 180 can later be removed from thesystem apparatus 100 through the capsule disposal door 117. Accordingly,each capsule 102 is discarded after a single use.

Referring now to FIGS. 14A to 27, another embodiment 200 of theinvention is shown. In this embodiment the product container is ahypodermic syringe, which optionally may be used directly for injection.

Referring more specifically now to FIGS. 14 A and 14B, housing 210includes two parts: housing portion 210 a and housing portion 210 b.Housing portion 210 a includes a lid 211 on its upper surface forcapsule loading, LCD display 212 and keypad 213 on the front surface, avent 214 and a door 218 for spent capsule disposal. Housing portion 210a also includes sections 219 in which the electrical components andmicroprocessor(s) are situated. Sections 219 can be opened to provideaccess to the system electronics. Housing section 210 b extendslaterally from a side of housing section 210 a and includes a lid 215for loading a hypodermic syringe, a door 216 for a label printer 270(FIG. 15), and a slot 217 for printed labels.

Referring to FIG. 15, system apparatus 200 includes a frame 220 and aplatform 221 for supporting the components described below.

Referring also now to FIGS. 16 to 18, in the housing portion 210 a thereis positioned the inventory structure 230 which comprises a non-movablecarousel body 231 having a plurality of chambers 232 arranged around acircumferential periphery of the carousel body 231 and extending fromthe top of the carousel body 231 to the bottom. The chambers 232 areeach adapted to hold a plurality of pharmaceutical agent-containingcapsules 202 in a top to bottom array. The capsules each have a prolatebody portion 203 fabricated from a sturdy plastic, which may be eitherflexible or rigid. However, the end 204 of the capsule is configuredwith a resilient film such as rubber adapted to be easily penetrated bya hypodermic needle so as to permit transfer of the pharmaceutical agentfrom the capsule 202 to a hypodermic syringe. The chambers 232 areradially oriented and configured to hold elongated capsules in a lateralorientation such that the ends 204 of the capsules face radiallyoutward. The chambers 232 can have a linear and/or zig-zagconfiguration. The zig-zag configuration allows for the storage of morecapsules than the linear shape and provides for greater control of themovement of the capsules. In an embodiment as shown in FIG. 18 thechannels 232 are zig-zag shaped.

Referring to FIG. 23, beneath the carousel body 231 is a workingcylindrical plate 241 having a plurality of notches 242 disposed aroundthe circumferential periphery of the plate 241, each notch 242 beingconfigured and dimensioned to hold a single capsule 202 in a radialconfiguration. The notches 242 can be aligned with channels 231 topermit the bottommost capsule 202 in a channel to drop into acorresponding notch. The working cylindrical plate is rotatable andadapted move selected capsules into a processing area as describedbelow. The capsules can roll or slide on the blocking plate 243 belowthe working cylindrical plate 241 as the working plate 241 rotates.

Referring to FIGS. 23, 24, 26 and 27, beneath the working cylindricalplate 241 is a preferably non-rotatable blocking plate 243 whichprevents the capsules 202 in the notches 242 from dropping out of thenotches. However, the blocking plate 243 includes a gate 244, which ismovable between a closed position and an open position. When gate 244 isin the open position and a notch 242 is aligned with the gate 244, anycapsule in the notch is allowed to drop through the gate and into thespent capsule discard bin 280. Accordingly, after the pharmaceuticalagent has been drawn out of a capsule, the working plate is rotated tomove the notch with the spent capsule into alignment with the gate 244,the gate 244 is then opened and the spent capsule is discarded into thespent capsule discard bin 280 for subsequent removal from the systemapparatus 200. A motor 246 positioned beneath platform 221 in thehousing portion 210 a (FIG. 15) rotates the working cylindrical plate241 in response to operating instructions.

Referring also to FIGS. 19 to 22, housing portion 210 b includes meansfor puncturing the capsules and drawing off the pharmaceutical agenttherefrom. In particular, hypodermic syringe support frame 260 isadapted to receive and move a hypodermic syringe 290 as well as tooperate the hypodermic syringe so as to draw pharmaceutical agentdirectly from the capsule into the syringe chamber 294. The syringe 290initially has a protective cap 293 covering the hypodermic needle 291 toprevent accidental needle sticks (FIG. 19). Referring also now to FIGS.25A to 25G, the syringe 290 is first loaded into the support frame 260such that the syringe chamber 294 is secured is secured in the supportframe 160 and the end of the syringe plunger 292 is engaged in theplunger grasper 264. The hypodermic syringe support frame 260 is thenmoved forward by a first linear actuator 261 from a first loadingposition to a second position wherein a cap remover 263 engages andholds the protective cap 293 (FIG. 25B). A solenoid 262 actuates theclasping mechanism of the cap remover 263 to releasably lock the cap293. The linear actuator 261 then moves the hypodermic syringe 290 in areverse direction to a third position to disengage the protective cap293 from the hypodermic syringe 290 (FIG. 25C). The cap remover 263 isthen moved upward by a second linear actuator 265 such that it is nolonger in the way of further advancement of the hypodermic syringe 290advancement (FIG. 25D). The first linear actuator 261 then advances thehypodermic syringe to a fourth position where the hypodermic needlepunctures the end 204 of the pharmaceutical agent-containing capsule 202in the processing area (FIG. 25E). The plunger grasper 264 is then movedbackwards by a third linear actuator 266 to create a negative pressurein the syringe chamber 294, thereby drawing pharmaceutical agent fromthe capsule 202 and into the hypodermic syringe 290 (FIG. 25F). Aquantity of the transferred solution can be controlled by travellingdistance of the plunger 292 considering volume of the loaded syringechamber 294. The first linear actuator 261 then moves the hypodermicsyringe 290 backwards to a fifth position to withdraw the needle 291from the processing area. Referring also now to FIG. 27, the workingplate 241 is then rotated to position the spent capsule 202 over thegate 244, which is then opened to drop the spent capsule into thediscard bin 280. If another capsule is to be used the workingcylindrical plate 241 is then moved to position the new capsule in theprocessing area for puncture by the hypodermic needle 291 and the abovedescribed procedure is repeated. If no further capsules are to be used,the cap holder 263 is dropped down to a position wherein the protectivecap 293 in alignment with the needle 291. The hypodermic syringe is thenadvanced again to engage the protective cap 293 with the hypodermicneedle 291, the protective cap 293 is then released, and the firstlinear actuator moves the entire hypodermic syringe 290 backwards. Theuser can then remove the loaded hypodermic syringe, which is preparedfor injection treatment of a patient. The label printer 270 can printout a label to be associated with the hypodermic syringe 290 to identifythe contents of the hypodermic syringe 290, the patient, and any otherappropriate information. The information can be printed out as text, barcode or quick response (qr) code.

Referring now to FIGS. 28 to 34B, another embodiment 300 of theinvention is shown.

Referring more specifically to FIG. 28, housing 310 includes a lid 311on its upper surface for capsule loading, LCD display 312 and keypad 313on the front surface, a vent 314, a door 317 for spent capsule disposal,a door 318 for waste solution disposal, a transparent cover wall 315,and doors 316 for providing access to an internal chamber 322 forplacement of the product vial 390. The product vial 390 is placed inchamber 322 over a fluid drain 382 for spent fluid (FIG. 34A). Housing310 also includes openable sections 319 in which the electricalcomponents and microprocessor(s) are situated.

Referring to FIGS. 29A and 29B, system apparatus 300 includes a frame320 and a platform 321 for supporting the components described below.Referring also now to FIG. 30, in the housing 310 there is positionedthe inventory structure 330, which comprises a non-movable carousel body331 having a plurality of chambers 332 arranged around a circumferentialperiphery of the carousel body 331 and extending from the top of thecarousel body 331 to the bottom. The chambers 332 are each adapted tohold a plurality of pharmaceutical agent-containing capsules 302 in atop to bottom array. The capsules each have a generally cylindrical bodyportion 303 fabricated from a sturdy puncture resistant plastic, whichmay be either flexible or rigid. However, the end 304 of the capsule isconfigured with a resilient film such as rubber adapted to be easilypenetrated by a hypodermic needle so as to permit transfer of thepharmaceutical agent from the capsule 302 to a product vial 390 (FIGS.33A and 33B). The chambers 332 are radially oriented and configured tohold elongated capsules 302 in a lateral orientation such that the ends304 of the capsules face radially outward. In an embodiment the chambers232 are zig-zag shaped although they can also be linear, or part linearand part zig-zag.

Referring to FIG. 31, beneath the carousel body 331 is a means forselecting a capsule and moving the capsule to a processing area whichincludes a working cylindrical plate 341 having a plurality of notches342 disposed around the circumferential periphery of the plate 341, eachnotch being configured and dimensioned to hold a single capsule 302 in aradial configuration. The notches 342 can be aligned with channels 331to permit the bottommost capsule 302 in a channel to drop into acorresponding notch 342. Notches 342 preferably have inward directedridges 342 a, which constrict the radial opening 342 b of the notch toprevent the capsule 302 from sliding out of opening 342 b. The workingcylindrical plate 341 is rotatable, and adapted move selected capsulesinto a processing area as described below. The capsules can roll orslide on the blocking plate 343 below the working cylindrical plate 341as the working plate 341 rotates.

Beneath the working cylindrical plate 341 is a preferably non-rotatableblocking plate 343, which prevents the capsules 302 in the notches 342from dropping out of the bottom of notches 342. However, the blockingplate 343 includes a gate 344, which is movable between a closedposition and an open position. When gate 344 is in the open position anda notch 342 is aligned with the gate 344, any capsule in the notch isallowed to drop through the gate 344 and into the spent capsule discardbin 380 through opening 381 in platform 321. Accordingly, after thepharmaceutical agent has been drawn out of a capsule 302, the workingplate 341 is rotated to move the notch 342 with the spent capsule intoalignment with the gate 344, the gate 344 is then opened and the spentcapsule is discarded into the spent capsule discard bin 380 forsubsequent removal from the system apparatus 300 through door 317 in thehousing. A motor 346 positioned beneath platform 321 in the housingportion 310 (FIG. 29A) rotates the working cylindrical plate 341 inresponse to operating instructions.

Referring also now to FIGS. 31, 32A, 32B, 33A and 33B, the workingcylindrical plate is rotated to move a selected capsule 302 to aprocessing area wherein the capsule is aligned with a means forpuncturing the capsule and transferring the pharmaceutical agent fromthe capsule to the product vial. More specifically, the apparatus 300includes an extraction needle 361, which is moved by solenoid 362 from aposition wherein the extraction needle is spaced apart from the end 304of the capsule to a position wherein it punctures the end 304 of thecapsule. The pharmaceutical agent is drawn out of the capsule by anegative pressure through a fluid line 371. A pinching valve 372regulates the flow of fluid through the fluid line 371. In order todevelop the negative pressure to withdraw the pharmaceutical agent, asshown in FIGS. 33A and 33B, an injection nozzle 374 and vacuum channel375 mounted to a piston 377 are aligned with a product vial 390positioned within product vial chamber 322 (FIG. 28) and moved by linearactuator 373 (FIGS. 29A and 29B) from an upper position wherein theinjection nozzle 374 and vacuum channel 375 are spaced apart from theproduct vial 390 to a lower position wherein the injection nozzle 374and vacuum channel 375 penetrate a rubber seal at the top end 391 of theproduct vial 390 (FIGS. 33A and 33B). The vacuum channel 375 ispreferably shorter than the injection nozzle 374. In an embodiment theinjection nozzle can be moved laterally to align the injection nozzlewith the product vial. The vacuum channel 375 is connected by a vacuumline to a vacuum pump 376 (FIGS. 32A and 32B), which is actuated to drawa vacuum in the interior of the product vial 390. This vacuum then drawsthe fluid pharmaceutical agent from the capsule 302 through the fluidline 371 and injection nozzle 374, and into the product vial. A quantityof the transferred solution can be controlled by power of the vacuumpump 376 and transporting time which is regulated by the valve 372. Whenthe contents of one capsule have been transferred it is moved over gate344 and dropped into the spent capsule discard bin 380. If anothercapsule is to be used the process is repeated. If no more capsules 302are to be used the injection nozzle 374 is withdrawn upward and theproduct vial 390 removed from product vial chamber 322, which uncoversfluid drain 382 in product vial chamber 332.

Referring also now to FIGS. 34A and 34B, the system is then flushed withan antiseptic cleaning fluid. The injection nozzle 374 is moved downwardsuch that it at least partially enters fluid drain 382. A capsule 302containing a cleaning fluid of, for example, ethanol and/or deionizedsterile water is punctured as described above and the pressure forcesthe cleaning fluid through the system whereupon it exits the injectionnozzle 374 and passes through the fluid drain 382 having a rubber filmwhich is penetrated by the injection nozzle, and into a spent fluidcontainer (not shown). The accumulation of spent fluid in the containercan be removed through door 318 in the housing and discarded. An annularrecess around the mouth of the fluid drain 382 can be dimensioned so asto receive the bottom of the product vial and thereby serve as a vialretainer to stabilize the product vial.

In an alternative embodiment of system apparatus 300, all of thepharmaceutical agent-containing capsules can be pressurized. Althoughsuch an alternative will be similar to embodiment 300 described above,in this alternative embodiment, the vacuum pump 376 and vacuum channel375 can be omitted as the withdrawal of the pharmaceutical agent will beaccomplished by positive pressure. A quantity of the transferredsolution can be controlled by the valve 372 since the pressure insidethe capsules is pre-determined and packaged.

Referring now to FIG. 35, in an embodiment the capsule as illustrated bycapsule 503 can have a rectangular body with an elliptical cross-section503 a and an end 503 b of resilient rubber material.

FIG. 36 illustrates the application of positive pressure in a verticaldirection to a capsule 504 to expel pharmaceutical agent therefrom. Thecapsule 504 is securely held between jaws 511 a and 511 b of clampingmechanism 511.

FIGS. 37A and 37B illustrate the application of lateral positivepressure to a capsule to expel pharmaceutical agent therefrom by jaws512 a and 512 b of a caliper mechanism. In FIG. 37A jaw 512 b isstationary while jaw 511 a is moved to apply pressure to the capsule504. In FIG. 37B both jaws 512 a and 512 b are moved.

FIG. 38 illustrates the placement of sensors 520 in apparatus 100 tomonitor the quantity of capsules loaded into racks 131.

FIG. 39 illustrates the placement of sensors 521 to monitor capsuleloading below the racks 131 at the loading slide, gate 141.

FIG. 40 illustrates the placement of sensors 522 along the guide channel154 to monitor capsule loading in the conveyor system, belt 151, andalso illustrates the placement of sensors 523 at the processing areawhere the capsules are squeezed and punctured.

FIG. 41 illustrates the placement of sensors 524 a to monitor thelifting of the product vial 103 on the loading platform 161 by crank 162to puncture the capsule.

FIG. 42 illustrates the placement of sensors 524 b to monitor thelateral movement of the product vial 103 on the loading platform 161;

FIGS. 43A, 43B, 43C and 43D illustrate the placement of sensors 525,526, 527 and 528 at lid 111, printer door 114, capsule disposal door 117and vial loading door 119, respectively, to monitor the open or closedposition of the doors.

FIG. 44 illustrates the loading of channel members 132 in linear notches531 of a carousel shaped inventory structure 530 instead of verticalracks 131.

While the above description contains many specifics, these specificsshould not be construed as limitations of the invention, but merely asexemplifications of preferred embodiments thereof. Those skilled in theart will envision many other embodiments within the scope and spirit ofthe invention as defined by the claims appended hereto.

What is claimed is:
 1. A system for compounding agents for topicaltreatment of a subject, which comprises: a housing enclosing an interiorspace; an inventory structure having a plurality of chambers forindividually holding one or more agent-containing single use capsules,wherein each capsule has a volume capacity of from about 0.1 to about10.0 mL liquid; means for selecting capsules in accordance withpredetermined agents contained in said capsules; means for moving theselected capsules to a processing area; means for sequentiallytransferring a controlled quantity of the predetermined agent withdirect fluid communication from each selected capsule to a productcontainer under positive or negative pressure; and means forautomatically discarding spent capsules from which the agents have beenremoved after a single use, wherein the means for transferring the agentcomprises a means for mechanically compressing the capsule to provide apositive external pressure for forcing the agent from the capsulethrough a needle and into the product container.
 2. The system of claim1, further comprising means in the processing area for puncturing theselected capsules.
 3. The system of claim 1, wherein the chambers of theinventory structure comprise a plurality of vertical racks forindividually holding a plurality of channels members, each channelmember holding a plurality of capsules in a vertical array, and eachchannel member having a bottom end.
 4. The system of claim 3, whereinthe means for selecting capsules comprises a capsule separationmechanism at the bottom end of each channel, the capsule separationmechanisms being individually movable between a first position whereinthe bottom end of the respective channel is closed to prevent passage ofa capsule through the bottom end of the channel, and a second positionwherein the bottom end of the channel is open to permit passage of acapsule therethrough.
 5. The system of claim 1, wherein the means formoving the selected capsules to the processing area comprises a lineartransport system.
 6. The system of claim 2, wherein the productcontainer is a product vial and the means for puncturing the capsulecomprises: a cap applied to the product vial, the cap possessing aneedle and an air vent; and, a mechanism for piercing the capsule withthe needle.
 7. The system of claim 1, wherein the means for discardingthe spent capsules comprises a waste bin positioned in the interior ofthe housing into which the spent capsules are dropped.
 8. The system ofclaim 1, wherein the inventory structure comprises a carousel, whereinthe chambers are arranged around a circumferential periphery of thecarousel, and the capsules are disposed within the chambers or in linearchannel members removably insertable in the chambers.
 9. The system ofclaim 8, wherein the chambers have a linear or zig-zag configuration.10. The system of claim 8, wherein the capsules have an elongatedcylindrical or prolate configuration and are horizontally or verticallyoriented in respective chambers.
 11. The system of claim 2, wherein themeans for puncturing the capsules comprises an extraction needle movablebetween a first position and a second position wherein the extractionneedle pierces the end of a selected capsule sufficiently to draw agenttherefrom.
 12. The system of claim 8, further comprising an injectionsystem positioned within the housing, the injection system comprising aninjection nozzle which is movable between an initial upper position anda lower position for insertion into the product container.
 13. Thesystem of claim 12, wherein the injection nozzle is also laterallymovable.
 14. The system of claim 12, further comprising a vacuum conduitassociated with the injection nozzle.
 15. The system of claim 12,further comprising a means for disposing waste produced by the cleaningof the injection system, wherein the means for disposing waste producedby the cleaning of the injection system comprises a drain leading to awaste solution container within the interior of the housing.
 16. Thesystem of claim 15, further comprising a means for cleaning theinjection system, wherein the means for cleaning the injection systemcomprises a capsule containing a sterile cleaning solution comprisingethanol and/or deionized water.
 17. The system of claim 14 furthercomprising a vacuum pump.
 18. The system of claim 1, wherein the productcontainer is a hypodermic syringe having a needle attached to one end, aplunger, and a removable cap covering the needle, and wherein the meansfor transferring the agent comprises mounting means for holding thehypodermic syringe, said mounting means being movable between a firstposition wherein the hypodermic syringe is spaced apart from theselected capsule to a second position wherein the needle penetrates thecapsule, wherein the mounting means further comprises means for graspingand pulling the plunger of the hypodermic syringe, and wherein thesystem further includes means for removing the cap.
 19. The system ofclaim 1, further comprising a UV sterilizing lamp positioned in theinterior of the housing.
 20. The system of claim 1, wherein the agentscomprise one or more of vitamins, growth hormone, glucosamine, omega-3fatty acids, onabotulinumtoxin A and/or insulin.
 21. The system of claim1, wherein the capsules and chambers are color coordinated.
 22. Thesystem of claim 1, further comprising a plurality of sensors positionedin the interior of the housing for monitoring the capsule inventory andoperation of the system.
 23. The system of claim 1, further comprising alabel printer.
 24. The system of claim 1, wherein the capsules arepressurized.
 25. The system of claim 1, further comprising informationinput and output units.
 26. The system of claim 1 wherein the agentscomprise one or more of vitamins, growth hormone, glucosamine, omega-3fatty acids, onabotulinumtoxin A, and/or insulin, and the subject is ahuman or animal.
 27. A method for compounding agents for topicaltreatment of a subject, comprising: storing a plurality ofagent-containing capsules in an inventory structure; selecting one ormore capsules according to the agents contained therein; puncturing theselected capsules with an extraction device; withdrawing a quantity ofagents from the selected capsules under positive or negative pressureand transferring the withdrawn agents to a product container; discardingspent capsules from which the agents have been withdrawn after a singleuse of the capsules, wherein the transferring the withdrawn agents to aproduct container comprises using a means for mechanically compressingthe capsule to provide a positive external pressure for forcing theagent from the capsule through a needle and into the product container.